Vascular Atp Diphosphohydrolase (Cd39/Atpdase)

Circulatory homeostasis is usually maintained by quiescent endothelial cells that possess highly effective anticoagulant and platelet thromboregulatory mechanisms. Following injury, the vascular endothelium is considered to undergo a process of activation where cells are exposed to oxidative stress, lose intrinsic antithrombotic properties and become procoagulant and facilitative for platelet aggregation. Endothelial cells express an ATPDase that hydrolyzes extracellular adenosine nucleotides and can inhibit stimulated human platelet aggregation in vitro. Loss of this ectoenzyme activity with reduced membrane protein expression occurs shortly following TNF alpha stimulation or perturbation of endothelial cells by reactive oxygen species in vitro. Comparable events follow reperfusion injury and xenograft rejection in vivo. Additionally, the administration of antioxidants and purified apyrases ameliorate rat renal reperfusion injury and discordant xenograft rejection, respectively.